Safety of Brucea javanica and Cantharidin Combined with Chemotherapy for Treatment of NSCLC Patients

Objective: To assess the safety of Brucea javanica and Cantharidin combined with chemotherapy in treatingpatients with non-small-cell lung carcinoma. Method: A consecutive cohort of patients with NSCLC were dividedinto four groups: experimental group A treated with Brucea javanica injection combined with chemotherapy;experimental group B with Cantharidin injection combined with chemotherapy; experimental group C treatedwith Brucea javanica and Cantharidin injection combined with chemotherapy; and the control group receivingonly chemotherapy. After more than two courses of treatment, safety, quality of life and side effects were evaluated.Results: The incidences of myelosuppression in groups A, B and C were lower than that in Control group (p<0.05),but without significant differences among A, B and C. Adverse effects on the gastrointestinal tract also werelower than in controls (p<0.05) without variation amnog the combined treatment groups. Conclusions: Bruceajavanica or Cantharidin combined with chemotherapy could in both cases improve quality of life in our cohortof NSCLC patients without any increase in toxicity. However, further clinical experiments should be conductedto evaluate the efficacy of Brucea javanica and Cantharidin combined with chemotherapy for patients withNSCLC.     

Cantharidin and demethylcantharidin (palasonin) content of blister beetles (Coleoptera: Meloidae) from southern Africa

In two species of meloid beetles, Hycleus oculatus and Hycleus tinctus, from southern Africa, cantharidin and demethylcantharidin (palasonin) were assayed quantitatively. For cantharidin the mean value per specimen was about 1 mg for H. oculatus and 0.2 mg for H. tinctus, the mean palasonin concentration was 20 (H. oculatus) and 12 times (H. tinctus) lower, respectively. However, considerable individual variation in the cantharidin concentration was observed and values of more than 6 mg of this compound per beetle were measured pointing to the high risk of severe and even fatal poisoning when ingesting these insects.     

Pharmacological properties of blister beetles (Coleoptera: Meloidae) promoted their integration into the cultural heritage of native rural Spain as inferred by vernacular names diversity,traditions, and mitochondrial DNA

Ethnopharmacological relevance

Beetles of the family Meloidae (blister beetles) are often reported in pharmacological literature because of their content of cantharidin. Cantharidin has a long history in human medicine and was commonly applied in the 19th and the early 20th centuries, although its use has been progressively abandoned since then. Contrary to most, even common, large species of Coleoptera, blister beetles of the genera Berberomeloe, Physomeloe and to a lesser extent Meloe, are usually recognized and often incorporated into local folk taxonomy by inhabitants of rural areas in Spain.

Aim of the study

To demonstrate the role that pharmacological properties of blister beetles must have played in their integration in the culture of early Iberian human societies, but also in the preservation of their identity until today, a rare case for Spanish insects. To achieve this purpose we document the diversity of vernacular names applied in rural areas of Spain, and we determine, using molecular data, the antiquity of the presence of two species of the better-known blister beetle in rural Spain, Berberomeloe majalis and Berberomeloe insignis.

Materials and methods

We try to document the extent of traditional knowledge of meloid beetles in rural areas by interviewing about 120 people from villages in central and southern Spain. We also use mitochondrial DNA sequences (Cytochrome Oxidase I and 16SrRNA) obtained from several populations of two species of the better known blister beetle in rural Spain, Berberomeloe majalis and Berberomeloe insignis, to determine whether these beetles were already present in the Iberian Peninsula when earlier ancient cultures were developing.

Results

Our results show that, based on mitochondrial DNA, blister beetles of the genus Berberomeloe were present in the Iberian Peninsula long before humans arrived, so ancient Iberian cultures were in contact with the same beetle species occurring now in rural areas. On the other hand, people interviewed in rural communities provided us with more than 28 different vernacular names, a few short songs incorporated to local folklore, and some therapeutic uses.

Conclusions

Current knowledge of blister beetles of the family Meloidae in rural Spain was likely developed as a consequence of their pharmacological properties; we hypothesize this knowledge was inherited from ancient pre-Christian Iberian native cultures as part of their traditional therapeutic traditions. It is possible then, that current vernacular names and traditional songs are the only remnants of an ancient knowledge of pharmacological uses of meloid beetles, verbally transmitted from the ancestral cultures to modern day rural Spain. Our work suggests that this legacy, part of the European Cultural Heritage, is disappearing fast, in parallel to the loss of traditional agricultural techniques.     

斑蝥酸钠对肝癌细胞HepG_2增殖抑制作用的研究

目的研究斑蝥酸钠（cantharidin,CTD）对人肝癌细胞HepG2增殖的抑制作用和机制。方法采用免疫组化染色法（I mmunohistochemistry,I H）和33528染色法观察斑蝥酸钠对HepG2细胞增殖的抑制作用,并观察肝癌细胞凋亡的形态学变化及不同剂量斑蝥酸钠对HepG2细胞凋亡率的影响。结果 1.0 mg/L以上斑蝥酸钠对人肝癌细胞HepG2的增殖有显著抑制作用（P〈0.01）,最高凋亡率（47.24%）出现于高剂量组（5.0 mg/L）。结论斑蝥酸钠对人肝癌细胞HepG2的增殖有显著抑制作用,是治疗肝癌较理想的药物之一。     

碱水提取斑蝥药材中斑蝥素的研究

目的建立碱性水溶液提取斑蝥药材中斑蝥素的提取方法,摆脱传统工艺中大量使用有机溶剂的限制,减少生产成本,降低环境污染。方法以斑蝥素的收率为考察目标,对碱水的浸泡次数及除杂时氨水的用量进行考察。结果采用气相色谱法测定提取液斑蝥素的含量。用碱水（8、5、5倍）3次处理斑蝥药材,药材提取液在用相当于斑蝥药材2.5倍的氨水碱化后去杂,提取澄明度较好,含量较高。结论通过实验比对,碱水药材提取率比药典方法检测率高,而且方法简便易行,实用价值高,为大生产提供依据。     

斑蝥素及衍生物抗肿瘤机制的研究进展

斑蝥素具有抗癌作用,但其毒副作用较大,受限于临床应用。人工合成的斑蝥素衍生物作为一种新型抗癌药物,既保留了斑蝥素的抗肿瘤作用,又减轻了斑蝥素的毒副作用,应用于临床。综述了斑蝥素及其衍生物(去甲斑蝥素、斑蝥酸钠、去甲斑蝥酸钠等)的抗肿瘤机制,为人类更好地利用斑蝥素资源提供理论基础。     

Inhibitory Effect of Cantharidin on Proliferation of A549 Cells

Objective:To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism.Methods:MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle.Results:Cantharidin showed inhibition against the proliferation of A549 cells,and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly.Conclusion:Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.     

三种抗肿瘤中药有效成分对人脐静脉内皮细胞生长的影响

目的探讨蜂毒素、去甲斑蝥素、蟾毒灵3种抗肿瘤中药提取物的抗血管生成作用,并检测其量效关系,比较其抑制血管生成所需浓度与抑瘤浓度的关系。方法采用四甲基偶氮唑蓝(MTT)法测定3种药物在不同浓度、时间对人肝癌细胞ECV304生长的抑制作用,计算半数抑制浓度(IC50),观察量效、时效关系。结果 3种药物对ECV304细胞的生长有不同程度抑制作用(P<0.05或P<0.01),且呈浓度和时间的依赖性。蜂毒素在24、48和72h抑制ECV304细胞的IC50分别为7.64、4.25和2.64μg/ml,去甲斑蝥素为271.52、108.83和80.76μg/ml,蟾毒灵为1.104、0.355和0.0905μg/ml。结论蜂毒素、去甲斑蝥素、蟾毒灵有明确的抑制血管内皮细胞增殖、抗血管生成的作用。